Pall Kleenpak™ Nova Filter Capsules Validation Guide

Brand: Pall

Model: Kleenpak™ Nova Filter Capsules

Type: Validation Guide

Validation Guide

Validation Guide for

Pall 'Kleenpak' Nova Filter Capsules

USTR 2099

Contents

1. Validation Overview 2

1.1 Introduction 2

1.2 Summary of conclusions 2

2. Burst testing 4

2.1 Introduction 4

2.2 Summary of methods 4

2.3 Results 4

2.4 Conclusions 6

3. Creep-rupture testing 6

3.1 Introduction 6

3.2 Summary of methods 6

3.3 Results 7

3.4 Conclusions 7

4. Pressure fatigue testing 8

4.1 Introduction 8

4.2 Summary of methods 8

4.3 Results 8

4.4 Conclusions 8

5. Environmental testing 9

5.1 Introduction 9

5.2 Summary of methods 9

5.3 Results 9

5.4 Conclusions 9

6. Filter/capsule seal testing 10

6.1 Introduction 10

6.2 Summary of methods 10

6.3 Results 11

6.4 Conclusions 12

7. Determination of water flow characteristics 13

7.1 Introduction 13

7.2 Summary of methods 13

7.3 Results 13

7.4 Conclusions 13

8. Extractables testing 14

8.1 Introduction 14

8.2 Summary of methods 14

8.3 Results 14

8.4 Conclusions

9. Shelf life studies 15

9.1 Introduction 15

9.2 Summary of methods 15

9.3 Results 15

9.4 Conclusions

10. Biological safety tests 18

10.1 Introduction 18

10.2 Summary of methods 18

10.3 Results 19

10.4 Conclusions 19

Appendix 1. Copy of Biological Safety test report 20

1. Validation Overview

1.1 Introduction

This report contains data applicable to ‘Pall’ ‘Kleenpak’ Nova filter capsules. These filter capsules have

integrally moulded inlet and outlet connections and precision-moulded vent and drain fittings.

The purpose of this report is to document the testing that has been performed to demonstrate the

strength and suitability of the capsules for use in pharmaceutical filtration applications.

Kleenpak Nova filter capsules incorporate standard 25cm (10") Pall filter cartridges and are available

with a number of different membrane types. Information about the validation of the different Pall

filter membranes is available in separate validation guides.

Kleenpak Nova filter capsules with a ‘G’ designation in the part number are provided non-sterile.

Depending on the filter membrane incorporated in the filter capsules, some versions are suitable for

gamma-irradiation by the user. Further details about the tolerance of different Pall membranes to

gamma-irradiation are available from your local Pall Sales company or distributor.

1.2 Summary of conclusions

Burst testing

Forty-nine Kleenpak Nova capsules were burst pressure tested and in all cases the burst pressures were

≥16.6 bar (240 psi), thereby fulfilling the required 5:1 safety ratio between burst pressure and the

maximum recommended operating pressure of 3 bar (43.5 psi). This testing included untreated

samples, samples that had been exposed to repeated autoclave cycles at 125OC and samples that had been

exposed to gamma-irradiation at doses of approximately 35 and 50 kGy.

Creep rupture testing

Kleenpak Nova filter capsules have been designed to be capable of operating at up to 3 bar (43.5 psi) for

168 hours (1 week) in continuous use. In order to allow for integrity testing the capsules have also been

designed to be capable of operating at up to 5.9 bar (85 psi) for a maximum of 10 hours.

The creep-rupture data presented using typical Kleenpak Nova capsules demonstrates the very large

safety margins that have been incorporated into these pressure claims.

Pressure fatigue testing

Kleenpak Nova filter capsules can withstand repeated pressurisation cycles, as demonstrated by fatigue

testing where typical capsules were exposed to 100,000 pressure cycles from 0 to 3 barg (43.5 psi) and

back to 0 barg again.

Environmental testing

The data presented provide assurance that Kleenpak Nova filter capsules will not be damaged by

extremes in temperature that they could potentially be subjected to during storage or transit.

Filter/capsule seal testing

The integrity of the filter/housing seal of Kleenpak Nova filter capsules has been demonstrated

by performing Forward Flow integrity tests and liquid bacterial challenge tests on filter samples that

have been exposed to either autoclave sterilisation or gamma-irradiation at doses of approximately

35 or 50 kGy.

Water flow characteristics

The water flow / pressure drop data presented for empty Kleenpak Nova filter capsules can be used in

conjunction with the pressure drop characteristics of standard 25cm (10") Pall filter cartridges to form

the basis for sizing filter systems employing Kleenpak Nova filter capsules.

Extractables testing

The level of aqueous and ethanol extractables for empty Kleenpak Nova filter capsules, irradiated with

doses of up to 53.0 kGy were found to be extremely low. Out of 12 extraction tests performed the

non-volatile residue extracted was ≤1 mg when water was used as the extraction fluid and ≤6 mg when

96% ethanol was used as the extraction fluid.

Actual service life may impose different conditions, such as different exposure times, temperature,

liquid purity etc. Evaluation under actual process conditions is therefore also recommended.

Shelf life studies

Burst pressure tests performed on irradiated Kleenpak Nova filter capsules that had been stored for up

to six months demonstrated that a high safety factor was maintained between the burst strength and the

maximum recommended operating pressure.

Microbial challenge tests demonstrated that irradiated filter cartridges incorporating ‘Ultipor’ ‘N66’

NFZ-grade membrane and ‘Fluorodyne’ II DFL-grade gave sterile effluent following four months

storage at room temperature (20 ± 5°C). Longer terms tests are in progress at time of writing.

Biological reactivity tests

Kleenpak Nova filter capsules were found to meet the requirements of the current United States

Pharmacopoeia for Class VI-121OC Plastics.

2. Burst testing

2.1 Introduction

The purpose of these tests was to demonstrate that Kleenpak Nova capsules withstand the maximum

pressure rating of 3 bar (43.5 psi) with an appropriate safety margin. Burst tests were performed on

empty untreated Kleenpak Nova capsules and also on samples that had been autoclaved and gamma-

irradiated at doses of approximately 35 and 50 kGy.

2.2 Summary of methods

Standard empty Kleenpak Nova capsules from production were used for these tests. Prior to the burst

testing samples of the capsules were pre-treated with one of the conditions shown below:

•Six one-hour autoclave cycles at 125OC

•Gamma irradiated at a dose of approximately 35 kGy

•Gamma irradiated at a dose of approximately 50 kGy

Before the burst tests were performed the vent and drain valves were removed and replaced with

blanking plugs. The whole assembly was placed in a water bath at 40OC. The empty capsules were filled

with water and the outlet was blanked off. Prior to starting the burst tests the capsules were held

within the water for a minimum of 15 minutes to ensure that they had equilibrated with the water bath

temperature. The inlet of the water-filled capsule was then connected to a pressure source and the

upstream pressure was gradually increased until the filter capsule burst.

2.3 Results

The results of the burst pressure tests are shown in Tables 2-1 to 2-4. The average burst pressure of the

non-treated Kleenpak Nova capsules was found to be 22.3 bar (324 psi). After exposure to six one-hour

autoclave cycles at 125OC the average burst pressure fell slightly to 20.8 bar (301 psi). Exposure to

gamma-irradiation was also found to have an effect on the burst pressures of the Kleenpak Nova filter

capsules. The average burst pressure of samples exposed to approximately 35 kGy was 18.5 bar (269 psi)

and the average burst pressure after exposure to approximately 50 kGy was 18.8 bar (272 psi).

In all cases the measured burst pressures far exceeded the 5:1 ratio between burst pressure and the 3 bar

(43.5 psi) maximum recommended operating pressure that is the design requirement for the Kleenpak

Nova capsule.

Table 2-1. Burst pressures of non-sterilised Kleenpak Nova capsules

Table 2-2. Burst pressures of Kleenpak Nova capsules autoclaved

for 6 one-hour cycles at 125°C

Pall Kleenpak Nova Burst pressure

capsule serial number

PB550001 22.1 bar / 320 psi

PB550002 22.1 bar / 320 psi

PB550003 23.4 bar / 340 psi

PB550004 23.4 bar / 340 psi

PB554001 22.8 bar / 330 psi

PB554002 22.8 bar / 330 psi

PB554003 22.1 bar / 320 psi

PB554004 24.1 bar / 350 psi

PB554005 23.4 bar / 340 psi

PB555001 22.1 bar / 320 psi

PB555002 22.1 bar / 320 psi

PB555003 21.4 bar / 310 psi

PB555004 24.1 bar / 350 psi

PB555005 24.1 bar / 350 psi

PB556001 22.8 bar / 330 psi

PB556002 19.3 bar / 280 psi

PB556003 21.4 bar / 310 psi

PB556004 23.4 bar / 340 psi

PB556005 20.7 bar / 300 psi

PB557001 22.1 bar / 320 psi

PB557002 22.8 bar / 330 psi

PB557003 24.1 bar / 350 psi

PB557004 22.8 bar / 330 psi

PB557005 16.6 bar / 240 psi

Average burst pressure 22.3 bar / 324 psi

Pall Kleenpak Nova Burst pressure

capsule serial number

PB550010 20.3 bar / 295 psi

PB550015 20.0 bar / 290 psi

PB550018 21.0 bar / 305 psi

PB550027 22.1 bar / 320 psi

PB555045 20.7 bar / 300 psi

PB551001 21.4 bar / 310 psi

PB551011 21.0 bar / 305 psi

PB551010 20.7 bar / 300 psi

PB551009 20.7 bar / 300 psi

PB551002 20.7 bar / 300 psi

PB552006 21.4 bar / 310 psi

PB552002 20.7 bar / 300 psi

PB552007 20.7 bar / 300 psi

PB552005 20.0 bar / 290 psi

PB552008 20.0 bar / 290 psi

Average burst pressure 20.8 bar / 301 psi

2.4 Conclusions

Forty-nine Kleenpak Nova capsules were burst pressure tested and in all cases the burst pressures were

≥16.6 bar (240 psi), thereby fulfilling the required 5:1 safety ratio between burst pressure and the

maximum recommended operating pressure of 3 bar (43.5 psi). This testing included untreated

samples, samples that had been exposed to repeated autoclave cycles at 125OC and samples that had been

exposed to gamma-irradiation at doses of approximately 35 and 50 kGy.

3. Creep-rupture testing

3.1 Introduction

Creep testing was performed in order to demonstrate the strength and stability of Kleenpak Nova

capsule bodies over extended periods of time whilst under pressure.

3.2 Summary of methods

Typical Kleenpak Nova empty filter capsules were used for the tests. Prior to the creep-rupture testing

the capsules were autoclaved for six one-hour cycles at 125°C.

For the creep-rupture tests the capsules were immersed in a water bath held at 40°C. The capsules were

filled with the warm water and connected to a creep-rupture rig designed to maintain set pressures

within the inside of the capsule until failure of the capsule occurred. At this end point, the failure time

and mode was noted.

Table 2-3. Burst pressures of Kleenpak Nova capsules

gamma irradiated with a dose of 35.6 – 37.2 kGy

Table 2-4. Burst pressures of Kleenpak Nova capsules

gamma irradiated with a dose of 50.1 – 53.0 kGy

Pall Kleenpak Nova Burst pressure

capsule serial number

PB554016 19.3 bar / 280 psi

PB554021 18.3 bar / 265 psi

PB554008 17.2 bar / 250 psi

PB554009 19.3 bar / 280 psi

PB554010 18.6 bar / 270 psi

Average burst pressure 18.5 bar / 269 psi

Pall Kleenpak Nova Burst pressure

capsule serial number

PB554026 19.0 bar / 275 psi

PB554025 18.6 bar / 270 psi

PB554023 18.6 bar / 270 psi

PB554024 19.0 bar / 275 psi

PB554037 18.6 bar / 270 psi

Average burst pressure 18.8 bar / 272 psi

3.3 Results

The results are shown in Figure 3-1. The points on the graph represent the average values obtained from

testing a minimum of two empty Kleenpak Nova filter capsules at each pressure. The data has been

extrapolated to predict the creep-rupture of samples maintained at constant pressure for up to 10,000

hours (416 days). Based on this extrapolation, it can be expected that Kleenpak Nova filter capsules will

withstand approximately 1,000 hours (41 days) at 8.6 bar (125 psi) and 10,000 hours (416 days) at 6.9

bar (100 psi).

Figure 3-1. Mean creep rupture pressures for empty

Kleenpak Nova filter capsules

3.4 Conclusions

Kleenpak Nova filter capsules have been designed to be capable of operating at up to 3 bar (43.5 psi) for

168 hours (1 week) in continuous use. In order to allow for integrity testing the capsules have also been

designed to be capable of operating at up to 5.9 bar (85 psi) for a maximum of 10 hours.

The creep-rupture data presented using typical Kleenpak Nova capsules demonstrates the very large

safety margins that have been incorporated into these pressure claims.

••••

•

0.1 1 10 100 1000 10000

250

200

150

100

Time (hours)

Pressure (psi)

Pressure (bar)

4. Pressure fatigue testing

4.1 Introduction

The purpose of these tests was to demonstrate that Kleenpak Nova filter capsules can withstand repeat-

ed cycles of pressurisation up to the maximum recommended operating pressure of 3 bar (43.5 psi).

4.2 Summary of methods

Typical Kleenpak Nova empty capsules were used for the tests. Six samples with triclover inlet and

outlet connections were used (P1-option) and six samples with hosetail inlet and outlet connections were

used (P6-option).

The tests were performed using a hydraulic test stand specially designed to produce controlled and

repeated pressure pulses. The vent and drain valves of the capsules were closed and the capsule outlets

blanked off. Prior to fatigue testing the capsules were filled with mineral oil and connected to the

hydraulic test stand. The pressure of the oil within the capsules was cycled from 0 barg to 3 barg

(43.5 psi) and back to 0 barg in 4 seconds. The pressure cycles were repeated 100,000 times on each

Kleenpak Nova capsule tested.

On completion of the fatigue testing the Kleenpak Nova capsules were carefully examined to determine

if there was any visible evidence of leaks or damage.

4.3 Results

The fatigue test results are shown in Table 4-1. Twelve Kleenpak Nova capsules were tested and none

of them showed any visible signs of leak paths or damage after 100,000 pressure cycles of 0 to 3 barg

(43.5 psi).

Table 4-1. Results of fatigue testing for Kleenpak Nova capsules

4.4 Conclusions

Kleenpak Nova filter capsules can withstand repeated pressurisation cycles, as demonstrated by fatigue

testing where typical capsules were exposed to 100,000 pressure cycles from 0 to 3 barg (43.5psi) and

back to 0 barg again.

Pall Kleenpak Nova Signs of leak paths/damage following

capsule serial number exposure to 100,000 pressure

cycles from 0 to 3 barg (43.5 psi)

PB557011 None

PB557017 None

PB551006 None

PB551007 None

PB557018 None

PB551005 None

PB580002 None

PB586032 None

PB586033 None

PB586034 None

PB586023 None

PB586035 None

Triclover inlet/outlet

connections

(P1-option)

Hosetail inlet/outlet

connections

(P6-option)

Inlet/outlet

connection option

5. Environmental testing

5.1 Introduction

The purpose of these tests was to demonstrate that Kleenpak Nova filter capsules could withstand

extremes in temperature that they could potentially be exposed to during storage or transit.

5.2 Summary of methods

Typical Kleenpak Nova empty capsules were used for the tests. Three samples with triclover inlet and

outlet connections were used (P1-option) and three samples with hosetail inlet and outlet connections

were used (P6-option).

All of the samples were carefully examined for visual defects prior to leak testing. The leak tests were

performed by immersing the assemblies in water and pressurising the internal capsules with 3 bar

(45 psi) air pressure for one minute. The capsules were then dried and placed in an environmental

chamber where they were exposed to 25 cycles of the following conditions:

•Heated from ambient to 60°C

•Temperature held at 60°C for one hour

•Cooled from 60°C to – 40°C

•Temperature held at – 40°C for one hour

•Heated from – 40°C to 30°C

On completion of the 25 temperature cycles, the filter capsules were inspected, diameter measurements

were made and then they were leak tested again using compressed air at 3 bar (45 psi).

5.3 Results

All of the capsules passed the leak testing before and after exposure to the thermal cycling (Table 5-1).

The capsules were carefully inspected and no signs of deformation, degradation or stress cracking were

observed.

Table 5-1. Results of environmental chamber testing

5.4 Conclusions

The data presented provide assurance that Kleenpak Nova filter capsules will not be damaged by

extremes in temperature that they could potentially be subjected to during storage or transit.

Pall Kleenpak Nova Signs of leak paths/damage following

capsule serial number exposure to 25 cycles

of thermal cycling

PB557010 None

PB557016 None

PB557012 None

PB586042 None

PB586009 None

PB586010 None

Triclover inlet/outlet

connections

(P1-option)

Hosetail inlet/outlet

connections

(P6-option)

Inlet/outlet

connection option

6. Filter/capsule seal testing

6.1 Introduction

The purpose of this series of tests was to confirm that the seal between the filter and the outer capsule

of Kleenpak Nova filters is integral. The testing of the seal was achieved by performing integrity and

bacterial challenge tests on typical Kleenpak Nova filter capsules. The testing was performed

on untreated samples and also on samples that had been exposed to gamma-irradiation at doses of

approximately 35 and 50 kGy.

6.2 Summary of methods

Standard Kleenpak Nova filter capsules incorporating 0.2m-rated Ulitpor N66 ‘Posidyne’ filter

membrane were used for the tests (part number NP6NFZP1G). Prior to challenge testing, six samples

were each subjected to one of the following conditions:

•One hour autoclave cycle at 125OC

•Gamma irradiation at a dose of approximately 35 kGy

•Gamma irradiation at a dose of approximately 50 kGy

The filter capsules were aseptically connected to the challenge apparatus shown schematically in

Figure 6-1 and subjected to a liquid bacterial challenge test using Brevundimonas diminuta (ATCC

19146) at a minimum challenge level of 1x107colony forming units per cm2of effective filtration area.

Figure 6-1. Bacterial challenge apparatus

Regulated air inlet

Pressure vessel with

aqueous suspension of

bacteria

Challenge filter

Drain

Analysis

membrane filter

During the challenge test, the entire filter effluent was passed through a 0.2µm-rated analysis disc on the

downstream side of the test filter assembly. The filter disc was incubated on agar and, following

incubation, the disc was examined to determine if bacteria had passed through the test filter during the

challenge. The titre reduction (TR) for each filter was determined as follows:

TR = Total number of organisms influent to the filter

Number of colonies recorded on the

downstream analysis disc

When no colonies were detected downstream, the titre reduction was expressed as:

>Total number of organisms influent to the filter (e.g. > 1 x 1011)

On completion of the challenge test the filter capsules were Forward Flow integrity tested.

6.3 Results

The results are shown in Tables 6-1 to 6-3. Each of the filters tested passed the Forward Flow integrity

test and gave sterile effluent when challenge tested with an aqueous suspension of B. diminuta.

Table 6-1. Forward Flow and bacterial challenge results for autoclaved Kleenpak

Nova filter capsules (part number NP6NFZP1G)

* Tested water wet, air test pressure 2760 mbar (40 psi), maximum allowable limit 12 ml/min

Table 6-2. Forward Flow and bacterial challenge results for Kleenpak Nova filter

capsules gamma-irradiated at 37.0 – 38.9 kGy (part number NP6NFZP1G)

* Tested water wet, air test pressure 2760 mbar (40 psi), maximum allowable limit 12 ml/min

Pall capsule Forward Flow* Sterile effluent Titre reduction

serial number (ml/min)

PB58301 2.7 Yes > 2.2 x 1011

PB583016 2.6 Yes > 2.4 x 1011

PB583017 3.4 Yes > 2.0 x 1011

PB583018 2.4 Yes > 2.3 x 1011

PB583021 1.8 Yes > 2.6 x 1011

PB583022 3.0 Yes > 2.6 x 1011

Pall capsule Forward Flow* Sterile effluent Titre reduction

serial number (ml/min)

PB583001 2.3 Yes > 2.8 x 1011

PB583004 2.1 Yes > 3.6 x 1011

PB583007 1.5 Yes > 3.7 x 1011

PB583008 2.0 Yes > 3.3 x 1011

PB583014 2.1 Yes > 3.3 x 1011

PB583025 1.8 Yes > 4.0 x 1011

Table 6-3. Forward Flow and bacterial challenge results for Kleenpak Nova filter

capsules gamma-irradiated at 52.7 – 53.5 kGy (part number NP6NFZP1G)

* Tested water wet, air test pressure 2760 mbar (40 psi), maximum allowable limit 12 ml/min

6.4 Conclusions

The integrity of the filter/housing seal of Kleenpak Nova filter capsules has been demonstrated by

performing Forward Flow integrity tests and liquid bacterial challenge tests on filter samples that

have been exposed to either autoclave sterilisation or gamma-irradiation at doses of approximately

35 or 50 kGy.

Pall capsule Forward Flow* Sterile effluent Titre reduction

serial number (ml/min)

PB583005 2.8 Yes > 1.7 x 1011

PB583006 3.8 Yes > 2.2 x 1011

PB583009 2.4 Yes > 2.4 x 1011

PB583010 2.5 Yes > 2.2 x 1011

PB583011 3.2 Yes > 2.5 x 1011

PB583027 2.0 Yes > 2.7 x 1011

7. Determination of water flow characteristics

7.1 Introduction

The purpose of these tests was to determine the pressure differential characteristics of Kleenpak Nova

filter capsules when subjected to different inlet water flow rates.

7.2 Summary of methods

The tests were performed on standard empty Kleenpak Nova filter capsules. Deionised water was

pumped through the filter capsules in the normal flow direction. Pressure transducers on the upstream

and downstream side of the assembly were monitored in order to calculate the differential pressure at

different water flow rates.

All of the data were corrected to a standard temperature of 20OC.

7.3 Results

The water flow/differential pressure characteristics of empty Kleenpak Nova filter capsules are shown in

Figure 7-1. Kleenpak Nova filter capsules are available with a range of different membrane types,

incorporating standard Pall 25cm (10”) filter cartridges. The water flow/differential pressure data

presented here can be used to provide guidance on filter sizing.

Figure 7-1. Water flow/differential pressure characteristics for empty

Kleenpak Nova filter capsules

7.4 Conclusions

The water flow / pressure drop data presented for empty Kleenpak Nova filter capsules can be used in

conjunction with the pressure drop characteristics of standard 25cm (10”) Pall filter cartridges to form

the basis for sizing filter systems employing Kleenpak Nova filter capsules.

0 10 20 30 40 50 60 70 80 90 100

450

400

350

300

250

200

150

100

-50

Water flow (litres/min)

Differential Pressure (mbar)

Differential Pressure (psi)

P6 option

hosetail inlet/outlet

P1 option

Triclover inlet/outlet

8. Extractables testing

8.1 Introduction

The purpose of these tests was to determine the amount of material that can be extracted from

irradiated typical Kleenpak Nova filter capsules by water and ethanol at ambient temperature.

8.2 Summary of methods

Typical Kleenpak Nova empty filter capsules were used for the tests. Prior to the extraction tests the

capsule samples were gamma-irradiated at doses of either approximately 35 or 50 kGy.

The extraction tests were performed by recirculating the extraction fluid (deionised water or 96%

ethanol) through the filter capsule for four hours. In order to minimise any background residues a

diaphragm pump with PTFE liquid contact parts and tubing was used. The non-volatile residue (NVR)

was determined by evaporating the extraction fluid to dryness. The material extracted from the

Kleenpak Nova filter capsules was compared with control samples of water and ethanol that had been

recirculated through the same extraction system but without the filter capsule installed.

8.3 Results

The results (Table 8-1) show the typical quantities of non-volatile residue extracted per Kleenpak Nova

capsule using deionised water and 96% ethanol at ambient temperature. The results reported are

typical for standard production capsules.

Table 8-1. Aqueous and ethanol extractables for Kleenpak Nova filter capsules

8.4 Conclusions

The level of aqueous and ethanol extractables for Kleenpak Nova filter capsules, irradiated with doses of

up to 53.0 kGy are extremely low. Out of 12 extraction tests performed the non-volatile residue

extracted was ≤1 mg when water was used as the extraction fluid and ≤6 mg when 96% ethanol was

used as the extraction fluid.

Actual service life may impose different conditions, such as different exposure times, temperature,

liquid purity etc. Evaluation under actual process conditions is therefore also recommended.

Extraction fluid Gamma irradiation

Kleenpak Nova Non-volatile

(kGy)

serial number residue (mg)

PB554006 0

PB554007 1

PB554022 1

PB554028 0

PB554036 0

PB554029 1

PB554012 0

PB554013 0

PB554019 0

PB554026 6

PB554034 5

PB554038 6

Water

96% ethanol

Extraction fluid Gamma irradiation Pall Kleenpak Nova Non-volatile

(kGy) capsule serial number residue (mg)

35.6 - 37.2

50.1 - 53.0

35.6 - 37.2

50.1 - 53.0

9. Shelf life studies

9.1 Introduction

There were two aims for this series of tests:

•To demonstrate that an adequate safety margin is maintained for the burst pressures of

gamma-irradiated Kleenpak Nova filter capsules following storage at room temperature for up to

six months

•To demonstrate that Pall N66 Posidyne and Fluorodyne II sterilising-grade membranes provide

sterile filtrate following storage for four months after exposure to gamma irradiation

9.2 Summary of methods

Burst pressure testing

Samples of typical Kleenpak Nova empty filter capsules were irradiated at a dose of approximately 35 or

50 kGy and then stored at ambient temperature for up to six months. On completion of the storage

interval, the burst pressures of the filter capsules were determined according to the method described

previously in Section 2.

Bacterial challenge testing

Typical AB1-style (25 cm) filter cartridges incorporating N66 Posidyne NFZ-grade membrane

and Fluorodyne II DFL-grade membrane (part numbers AB1NFZ7PH4 and AB1DFL7PH4) were

irradiated with doses of approximately 35 or 50 kGy. The filter cartridges were then stored in their

original packaging for four months at room temperature and then subjected to microbial challenge

testing according to the method described previously in Section 6.

9.3 Results

The results of the burst pressure tests performed on Kleenpak Nova filter capsules stored for up to 6

months following irradiation with doses of approximately 35 and 50 kGy are shown in Tables 9-1 and

9-2. In all cases the burst pressure measurements were ≥15.2 bar / 220 psi, thereby fulfilling the

required 5:1 safety ratio between burst pressure and the maximum recommended operating pressure of

3 bar (43.5 psi).

The results of the bacterial challenge tests performed on irradiated AB1-style filter elements in

corporating N66 Posidyne NFZ-grade membrane and Fluorodyne II DFL-grade that had been stored

for four months are shown in Tables 9-3 and 9-4. All of the filters tested produced sterile effluent

when challenged.

Table 9-1. Burst pressures of Kleenpak Nova capsules irradiated

at 35.6 – 37.2 kGy and then stored for up to 6 months

Table 9-2. Burst pressures of Kleenpak Nova capsules irradiated at

50.1 – 53.0 kGy then stored for up to 6 months

Pall Kleenpak Nova Burst pressure

capsule serial number

PB556014 20.0 bar / 290 psi

PB556018 17.2 bar / 250 psi

PB556022 18.6 bar / 270 psi

PB556020 19.3 bar / 280 psi

PB556015 19.3 bar / 280 psi

PB556019 16.6 bar / 240 psi

Average burst pressure 18.5 bar / 268 psi

PB556010 17.2 bar / 250 psi

PB556017 19.0 bar / 275 psi

PB556006 19.3 bar / 280 psi

PB556012 20.7 bar / 300 psi

PB556016 20.7 bar / 300 psi

Average burst pressure 19.4 bar / 281 psi

3 months

6 months

Storage time

Pall Kleenpak Nova Burst pressure

capsule serial number

PB556030 17.9 bar / 260 psi

PB556031 16.6 bar / 240 psi

PB556034 15.9 bar / 230 psi

PB556025 18.6 bar / 270 psi

PB556032 18.6 bar / 270 psi

PB556023 17.2 bar / 250 psi

Average burst pressure 17.4 bar / 253 psi

PB555032 19.3 bar / 280 psi

PB555023 18.6 bar / 270 psi

PB555026 19.3 bar / 280 psi

PB555027 19.3 bar / 280 psi

PB555029 15.2 bar / 220 psi

Average burst pressure 18.3 bar / 266 psi

3 months

6 months

Storage time

Table 9-3. Bacterial challenge results for N66 Posidyne grade NFZ filters

(part number AB1NFZ7PH4) stored for four months following irradiation

* Tested water wet, air test pressure 2760 mbar (40 psi), maximum allowable limit 12 ml/min

Table 9-4. Bacterial challenge results for Fluorodyne II grade DFL filters

(part number AB1DFL7PH4) stored for four months following irradiation

* Tested water wet, air test pressure 2760 mbar (40 psi), maximum allowable limit 12 ml/min

9.4 Conclusions

Burst pressure tests performed on irradiated Kleenpak Nova filter capsules that had been stored for up

to six months demonstrated that a high safety factor was maintained between the burst strength and the

maximum recommended operating pressure.

Microbial challenge tests demonstrated that irradiated filter cartridges incorporating N66 Posidyne

NFZ-grade membrane and Fluorodyne II DFL-grade gave sterile effluent following four months

storage at room temperature (20 ± 5°C).

Irradiation Pall filter Foward Flow* Sterile Titre reduction

dose serial number (ml/min) effluent

ID0859185 6.9 Yes > 1.5 x 1011

ID1090244 5.9 Yes > 2.2 x 1011

ID1090409 6.0 Yes > 2.0 x 1011

ID1090238 5.8 Yes > 1.9 x 1011

ID1090240 6.1 Yes > 2.5 x 1011

ID1090250 6.2 Yes > 2.1 x 1011

34.2 - 36.7 kG

45.4 - 49.4 kG

Irradiation Pall filter Foward Flow* Sterile Titre reduction

dose serial number (ml/min) effluent

ID0619124 1.9 Yes > 1.9 x 1011

ID0619650 3.0 Yes > 2.1 x 1011

ID0619131 3.4 Yes > 1.6 x 1011

ID0619565 2.6 Yes > 1.6 x 1011

ID0619663 3.5 Yes > 1.8 x 1011

ID0619618 2.2 Yes > 2.2 x 1011

34.2 - 36.7 kG

45.4 - 49.4 kG

10. Biological safety tests

10.1 Introduction

The purpose of these tests was to evaluate the biological suitability of the materials of construction of

the Kleenpak Nova filter capsules. The materials of construction are as follows :

Capsule components: Polypropylene

Valve and filter element seals: Silicone elastomer

10.2 Summary of methods

The tests were performed in accordance with the Biological Reactivity Tests in vivo for Class VI Plastics

(121°C) as described in the current United States Pharmacopeia. The tests were conducted by Gilbraltar

Laboratories, Inc., New Jersey, USA.

The testing procedures described in the USP include:

•Injection of extracts of plastic materials

•Implantation of the solid material into animal tissue

The four extracting media listed in the USP simulate parenteral solutions and body fluids.

These include:

•Sodium Chloride Injection

•1 in 20 Solution of Alcohol in Sodium Chloride Injection

•Polyethylene Glycol 400

•Vegetable Oil (sesame or cottonseed oil)

The USP states that extracts may be prepared at one of three standard conditions: 50°C for 72 hours,

70°C for 24 hours, or 121°C for 1 hour. The most stringent condition not resulting in physical changes

in the plastic is recommended, therefore the filters were extracted at 121°C.

Acute Systemic Injection Tests

An Acute Systemic Injection Test was performed to evaluate the potential of a single injection of an

extract to produce systemic toxicity. Sodium Chloride Injection and 1 in 20 Solution of Alcohol in

Sodium Chloride Injection were injected intravenously. Vegetable oil extract and Polyethylene Glycol

400 extract were injected intraperitoneally.

Intracutaneous Tests

An Intracutaneous Test was performed to evaluate the potential of a single injection of an extract to

produce tissue irritation. All four of the extracts listed above were used for these tests.

Intracutaneous Tests

An Intracutaneous Test was performed to evaluate the potential of a single injection of an extract to

produce tissue irritation. All four of the extracts listed above were used for these tests.

Implantation Tests

Implantation tests were also performed, in order to subject the materials of construction to the most

stringent conditions included in the USP. Each of the components of the Kleenpak Nova filter capsule

was implanted separately.

10.3 Results

The components of Kleenpak Nova filter capsules passed all of the tests specified. Appendix 1 shows a

copy of the test certificates.

10.4 Conclusions

Components of Kleenpak Nova capsules meet the requirements of the USP for Class VI -121°C Plastics.

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Pall Kleenpak™ Nova Filter Capsules Validation Guide

Brand: Pall

Model: Kleenpak™ Nova Filter Capsules

Type: Validation Guide

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Pall Kleenpak™ Nova Filter Capsules Validation Guide

Pall Kleenpak™ Nova Filter Capsules Validation Guide

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